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Jedruchniewicz, N.

Publications and source records attributed to Jedruchniewicz, N..

4 recordsLinked to original sources

A synthetic phageome reveals widespread and diverse human antibody responses to bacteriophages

Bacteriophages colonize humans, yet their recognition by humoral immunity remains unclear. We developed PhageScan, a PhIP- Seq platform comprising 277,051 phage and 49,630 human viral oligopeptides. Profiling sera from 192 healthy donors without prior phage therapy characterized anti-phage response specificity and revealed widespread, strong IgG reactivity to phages, comparable in prevalence and magnitude to that against human viruses. Recognition patterns were however highly individualized. Among phage sequences, 12,576 peptides were significantly enriched in at least two individuals. Strongly immunogenic epitopes preferentially originated from phages infecting pathogenic bacteria, whereas widely shared ''public'' epitopes were enriched among phages of environmental and food-associated bacteria. ImmE, a lactococcal phage endolysin recognized in 59.9% of individuals, showed reduced antibacterial activity in the presence of sera identified as ImmE-reactive by PhageScan, demonstrating functional relevance. These findings establish phage-directed antibodies as a widespread component of human immunity and PhageScan as a scalable platform for defining phage--antibody interactions.

immunology↗

Viral Burden: New insights into Estimating IgG Recognition Across Human Populations

Assessment of viral burden in populations is essential for understanding virus epidemiology and herd immunity potential. While serological profiling is straightforward at the individual level, it remains challenging at scale. We propose analysis advancing in serological technologies for broader population-level analysis and comparison. We used an epitope library in Phage Display ImmunoPrecipitation (PhIP) technology (VirScan type library) to assess IgG recognition of 49,630 representative viral oligopeptides in 134 serum samples from two populations (Poland and the US). Only 5.9% of oligopeptides were immunogenic, yet IgG recognition of viruses was consistent across populations - over 90% of virus species, 99% of genera, and 97% of families were detected. Shannon Diversity Index analysis supported these findings. Among immunogenic peptides, 9.1% were significantly more frequently recognized, though not correlated with recognition strength. We further proposed a normalization method to account for differences in viral proteome representation when assessing immune burden: the burden score. Finally, we demonstrated how this approach facilitates serological comparisons between populations. These observations show that while people are exposed to similar viruses, they produce antibodies against different viral epitopes. This individual variability, combined with broad virus recognition, likely strengthens population-level protection. Epitope recognition frequency seems to be shaped more by population exposure than by magnitude of response that an epitope can induce. Accurately measuring viral burden can inform healthcare planning, and antiviral technologies development.

immunology↗

Triadic Dynamics of Gastric Bacterial Microbiome, Phageome, and Host Genotype, with Implications for Disease Associations

The microbiota plays a key role for human health, and microbiome composition has been linked to specific health disorders many times. Different fractions of the microbiome enter dynamic interactions, particularly bacteria and bacteriophages (phages) - viruses preying on bacteria. Since the microbiome exists inside the human body, the body strongly affects the microbes, although not in a uniform way, but shaped by the extreme diversity of human genetic variants. These triadic dynamics of the bacterial microbiome, phageome, and human host genotype remain poorly understood; hence our goal in this study was to comprehend them as a holistic and interdependent system. Gastric biopsies were the source of the stomach microbiome (bacteria and phages). Genotyping of patients was conducted on blood samples. They were analyzed by next generation sequencing followed by multiway statistical comparisons of identified bacterial and phage taxa, human genetic variants, and medical data from the patients, including gastric disorder diagnostics. Commonly expected associations between presence of bacteriophages and their specific hosts were not found to be a universal principle. With comparable SNP correlations, the strongest associations between Staphylococcus and some staphylococcal phages or Enterobacteria and some enterobacteria phages were discovered. However, many more phage groups were not found to be clearly associated with their bacterial hosts, though often associated with SNPs, particularly those linked to immunological functions and body responses to bacteria and viruses. Thus, in addition to the expected effect on phage communities by shaping the communities of their bacterial hosts, the human body seems to affect phages directly, selecting for phages that survive its specific selective pressure, which can be defined by detection of particular genetic variants.

molecular biology↗

Identification of cross-reacting IgG hotspots to prevent immune evasion of SARS-CoV-2 variants

The major factor that shapes the global perspective for increase or diminution of successive pandemic waves of COVID-19 is the immunological protection. The SARS-CoV-2 virus constantly develops new variants, and capability of immune evasion is among the major factors that promote variant spreading in the human population. After two years of the pandemic and virus evolution, it is almost impossible to explain effects of all possible combinations different viral strains, a few types of vaccinations or new variants infecting an individual patient. Instead of variant-to-variant comparisons, identification of key protein regions linked to immune evasion could be efficient. Here we report an approach for experimental identification of SARS-CoV-2 protein regions that (i) have characteristics of cross-reacting IgG hot-spots, and (ii) are highly immunogenic. Cross-reacting IgG hot spots are regions of protein frequently recognized in many variants by cross-reacting antibodies. Immunogenic regions efficiently induce specific IgG production in SARS-CoV-2 infected patients. We determined four regions that demonstrate both significant immunogenicity and the activity of a cross-reacting IgG hot-spot in protein S, and two such regions in protein N. Their distribution within the proteins suggests that they may be useful in vaccine design and in serological diagnostics of COVID-19.

immunology↗